Marking the difference in acutely responding human CD8 T cells

The CD8 T cell response features functions that are fundamental for long-lasting immune protection, including antigen-specific cytolysis and memory. Accordingly, a range of differentiation subsets have been described with diverse functionalities and corresponding profiles of expression of markers. In both mouse and human systems, a major distinction has been “memory” versus “effector” terms. On the one hand, these terms may relate to temporality within the immune response : “effector” indicates the acute phase, “memory” refers to the post-contraction, resting phase. On the other hand, the terms also assign prototypic differentiation phenotypes that may be found at the same time-point : memory or effector subsets, based on characteristic markers. In this study, we analyse the human CD8 T cell response to YF-17D vaccination as the best-known model of acute immune response in humans. We study 21 characteristic markers conventionally used in mice and in humans to analyse and describe differentiation, activation, cycling, and so-called effector functions such as cytokine production and degranulation. We find clearly distinct 'acute traits' at the peak of the response that are shared amongst all non-naïve antigen-specific subsets, including in memory phenotype cells. These acute traits were low BCL-2 and high Ki67, CD38, HLA- DR, as well as increased Granzyme B and Perforin, which have been previously attributed only to effector cells at the peak of the response. Altogether, we evidenced 'acute traits' independent of differentiation phenotypes, supporting the semantic and marker distinction between “effector” and “acute” terms in the human CD8 T cell response. Overall design: Single cell ATAC sequencing of CD8 T cells derived from peripheral blood samples and sorted into different subsets: naïve, SCM or effector. Naive are polyclonal; SCM and effector either polyclonal or A2/LLW-specific. Three donors were sampled 14 days after YF-17D vaccination, i.e. at the peak of the acute phase of immune response. Three donors were sampled several years after YF-17D vaccination, i.e. in the long-term phase.